Increased Tumor Immune Microenvironment CD3+ and CD20+ Lymphocytes Predict a Better Prognosis in Oral Tongue Squamous Cell Carcinoma.

Raísa Sales De Sá,Marisol Miranda Galvis,Pablo Agustin Vargas,Luiz Paulo Kowalski,Clovis Antonio Lopes Pinto,Kenneth John Gollob,Alan Roger Santos-Silva,Oslei Paes Almeida,Bruno Augusto Linhares Almeida Mariz,Luciana Schultz,Amanda Almeida Leite

doi:10.3389/fcell.2020.622161

Abstract

Background: Oral tongue squamous cell carcinoma (OTSCC) causes over 350,000 cases annually and particularly impacts populations in developing countries. Smoking and alcohol consumption are major risk factors. Determining the role of the tumor immune microenvironment (TIME) in OTSCC outcomes can elucidate immune mechanisms behind disease progression, and can potentially identify prognostic biomarkers.Methods: We performed a retrospective study of 48 OTSCC surgical specimens from patients with tobacco and alcohol exposures. A panel of immunoregulatory cell subpopulations including T (CD3, CD4, CD8) and B (CD20) lymphocytes, dendritic cells (CD1a, CD83), macrophages (CD68), and immune checkpoint molecules programmed cell death protein 1 (PD-1) and ligand 1 (PD-L1) were analyzed using immunohistochemistry. The levels of immune effector cell subpopulations and markers were analyzed in relation to overall survival.Results: Pathological characteristics of the tumor microenvironment included inflammatory infiltrates (83.3%), desmoplasia (41.6%), and perineural invasion (50.0%). The TIME contained high levels of T cells (CD3+, CD4+, and CD8+) and B cells (CD20+), as well as immature (CD1a) and mature (CD83) dendritic cells, PD-1, and PD-L1. Higher numbers of TIME infiltrating CD3+ T cells and CD20+ B cells were predictive of better survival, while higher levels of CD83+ mature dendritic cells predicted better survival. CD3+ T cells were identified as an independent prognostic marker for OTSCC. Lastly, CD3+ T cells were strongly correlated with the number of CD8+ cells and PD-L1 expression.Conclusion: Our findings provide evidence that the TIME profile of OTSSC impacted prognosis. The high expression of CD3+ T cells and B cells are predictive of better overall survival and indicative of an immunologically active, inflammatory TIME in patients with better survival. The number of CD3+ T cells was an independent prognostic marker.

Highlights

Oral cancer is among the 10 most frequent cancers worldwide, with an incidence of over 350,000 new cases annually (Bray et al, 2018)
Our results demonstrated high prevalence of mature dendritic cells (CD83+) in the tumor microenvironment (TME) was correlated with an improved overall survival (OS) (HR 0.2, 95%CI 0.0–3.4) (p = 0.01) (Figure 4D)
Accumulating evidence suggests that Oral squamous cell carcinoma (OSCC) is an immunosuppressive disease, and immunotherapy has emerged as a novel approach to restore antitumor responses and to overcome escape mechanisms utilized by tumor cells (Ferris, 2015; Moskovitz and Ferris, 2018; Galvis et al, 2020)

Summary

Introduction

Oral cancer is among the 10 most frequent cancers worldwide, with an incidence of over 350,000 new cases annually (Bray et al, 2018). Oral squamous cell carcinoma (OSCC) of mucosal origin accounts for more than 90% of cases (Curado et al, 2016; Bray et al, 2018). Patients affected by oral tongue squamous cell carcinoma (OTSCC) are often elderly males over the sixth decade of life, with prolonged exposures to tobacco and alcohol (Scully and Bagan, 2009; Ng et al, 2017). Oral tongue squamous cell carcinoma (OTSCC) causes over 350,000 cases annually and impacts populations in developing countries. Determining the role of the tumor immune microenvironment (TIME) in OTSCC outcomes can elucidate immune mechanisms behind disease progression, and can potentially identify prognostic biomarkers

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Conclusion